Real Professor Moody

@petermoody.bsky.social

Macromolecular Crystallography, enzymology, particle accelerators, X-rays, neutrons, protons, electrons, motorcycles.

Absolutely delighted to have been included in this new twist to the story. Monooxygenase Activity of Indoleamine 2,3-Dioxygenase | Journal of the American Chemical Society pubs.acs.org/doi/10.1021/...

Monooxygenase Activity of Indoleamine 2,3-Dioxygenase

Indoleamine 2,3-dioxygenase (IDO) is a heme-dependent enzyme that catalyzes the first, rate-limiting step of the kynurenine pathway─the oxidation of l-tryptophan to N-formylkynurenine (NFK). IDO-catalyzed depletion of tryptophan levels and accumulation of kynurenine pathway metabolites is an important control mechanism of the immune responses in cells. IDO has been considered as a dioxygenase because two atoms of oxygen are inserted into the substrate. Here, we use LC-MS and NMR to examine the reactivity of human IDO (hIDO) with l-tryptophan (l-Trp) and several other tryptophan analogues. Alongside dioxygenase activity, we identify a concurrent pathway of heme-dependent monooxygenase activity in the reaction of hIDO with l-Trp, leading to the formation of a cyclic 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid (HPIC) species. Reaction profiles for the reaction of hIDO with other tryptophan analogues are likewise examined. Formation of HPIC from l-Trp is reproduced in HeLa cells induced to overexpress hIDO, indicating that this dual dioxygenase/monooxygenase reactivity also occurs biologically. Notably, the reaction of hIDO with β-[3-benzo(b)thienyl]-l-alanine (S-l-Trp)─a known inhibitor ─yielded only the cyclic HPIC analogue, suggesting that IDO activity can be selectively directed toward the monooxygenase pathway. Molecular dynamics simulations underscore the critical role of substrate plasticity within the active site of hIDO, while DFT calculations provide a mechanistic rationalization for the observed product distributions. Together, the data demonstrate dual dioxygenase/monooxygenase functionality for human IDO. As the overall gatekeeper for control of tryptophan levels in cells, the findings provide mechanistic information on relevance to therapeutic strategies focused on IDO inhibition.

pubs.acs.org

Looking to start your lab in generative biology / AI? Come join us at the @sangerinstitute.bsky.social Sanger is core-funded so you can generate data at scale to train the next generation of models and understanding. Design/Engineering/Chemistry/Proteins/Pathways! pls RT tinyurl.com/GenGenFaculty

Group Leader - Generative Biology and AI

Do you want to help us improve human health and understand life on Earth? Make your mark by shaping the future to enable or deliver life-changing science to solve some of humanity’s greatest challenge...

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Spread the word if you can. We have an unused stopped flow accessory from Applied Photophysics. We traded in our Chirascan CD instrument so we have no use for this anymore. Reach out if you are interested and can find a home for this setup. Will ofcourse only work with a Chirascan!

Bild

✒️ Parliament has been accused of an “outrageous abuse” that is “worthy of the Trump White House”, after refusing to issue us a media pass. Thousands have signed a petition calling on the government to give us access. Help defend press freedom, sign today. secure.declassifieduk.org/page/178447/...

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I stand with Declassified UK - I've just signed my name. Join me in telling Westminster that you care about freedom of the press.

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Can AlphaFold refine structures for X-ray & Cryo-EM/ET data? Now it can! Great collab with @moalquraishi.bsky.social and @randyjread.bsky.social led by @alisiafadini.bsky.social and @minhuanli.bsky.social. 🧵below. Code to follow...

Alisia Fadini@alisiafadini.bsky.social · last yr.

Structural biology is in an era of dynamics & assemblies but turning raw experimental data into atomic models at scale remains challenging. @minhuanli.bsky.social and I present ROCKET🚀: an AlphaFold augmentation that integrates crystallographic and cryoEM/ET data with room for more! 1/14.

Well over 600 signatories now. Please keep the momentum going. Sign and share to show how much the wider scientific community is concerned by the Royal Society's silence over Musk's FRS. Members of the UK and international scientific community are all welcome to sign.

Stephen Curry@scurry.bsky.social · last yr.

Now almost 450 signatories to my open letter calling on the @royalsociety.org to stand up for its values & deal with the widespread concerns raised by Elon Musk's Fellowship. Please consider signing & sharing: forms.gle/miDciq35oxyw... List of signatories here: occamstypewriter.org/scurry/2025/...

**ALERT** Just a couple of days left to apply for this PhD opportunity in the Hopkinson and Tanaka groups in Leicester. Evaluating the impact of chemically reactive metabolites in premature ageing BBSRC MIBTP studentship - 4 years fully funded www.findaphd.com/phds/project...

Evaluating the impact of chemically reactive metabolites in premature ageing at University of Leicester on FindAPhD.com

PhD Project - Evaluating the impact of chemically reactive metabolites in premature ageing at University of Leicester, listed on FindAPhD.com

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Great to see it out! Paper itself wouldn't be possible, of course, without a veritable horde of collaborators, and thanks very much for @jonlambert.bsky.social for writing such a wonderful commentary!

Philip Donoghue@phil-donoghue.bsky.social · 2y ago

Really nice commentary by Jonathan Lambert @jonlambert.bsky.social @quantamagazine.bsky.social about our study of the age and nature of LUCA, led by the awesome Ed Moody @emoody.bsky.social www.quantamagazine.org/all-life-on-...